Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479368 | SCV000566426 | uncertain significance | not provided | 2015-05-01 | criteria provided, single submitter | clinical testing | This deletion of 3 nucleotides in APC is denoted c.4328_4330delCTC at the cDNA level and p.P1443del at the protein level. The normal sequence, with the bases that are deleted in braces, is CCTC[CTC]AAAC. This in frame deletion of a single Proline residue occurs at a position that is conserved through mammals and is located in the 20-amino acid repeat ß-catenin binding domain (Azzopardi 2008). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider APC P1443del to be a variant of uncertain significance. |
| Ambry Genetics | RCV000567844 | SCV000667689 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-10 | criteria provided, single submitter | clinical testing | The c.4328_4330delCTC variant (also known as p.P1443del) is located in coding exon 15 of the APC gene. This variant results from an in-frame CTC deletion at nucleotide positions 4328 to 4330. This results in the in-frame deletion of a proline at codon 1443. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mendelics | RCV000708964 | SCV000838115 | uncertain significance | Familial adenomatous polyposis 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000708964 | SCV001200229 | uncertain significance | Familial adenomatous polyposis 1 | 2019-07-23 | criteria provided, single submitter | clinical testing | This variant, c.4328_4330del, results in the deletion of 1 amino acid(s) of the APC protein (p.Pro1443del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 418970). |